Experimental Exposure to Air Pollutants and Sympathetic Nerve Activity in Human Subjects (Particles)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Hannover Medical School
Sponsor:
Collaborator:
Fraunhofer-Institute of Toxicology and Experimental Medicine
Information provided by (Responsible Party):
Prof. Dr. Jens Jordan, Hannover Medical School
ClinicalTrials.gov Identifier:
NCT01914783
First received: July 30, 2013
Last updated: July 31, 2013
Last verified: July 2013
  Purpose

The primary hypothesis of the study is that in healthy elderly subjects experimental exposure to air pollutants increases sympathetic nervous system activity compared with sham (clean air) exposure. The secondary hypothesis of the study is that combined experimental exposure to air pollutants (particles + ozone) increases sympathetic nervous system activity to a greater extent than does the exposure to particles alone.


Condition Intervention
Cardiovascular Morbidity
Other: ultrafine particles
Other: ultrafine particles and ozone
Other: clean air

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Experimental Exposure to Air Pollutants and Sympathetic Nerve Activity in Human Subjects

Resource links provided by NLM:


Further study details as provided by Hannover Medical School:

Primary Outcome Measures:
  • Muscle sympathetic nerve activity (MSNA) [ Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone ] [ Designated as safety issue: No ]
    Change of sympathetic vasoconstrictor nerve activity directed to skeletal muscle expressed as sympathetic bursts per minute. The primary hypothesis of the study is that in healthy elderly subjects experimental exposure to air pollutants increases sympathetic nervous system activity compared with sham (clean air) exposure.


Secondary Outcome Measures:
  • MSNA burst incidence [ Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone ] [ Designated as safety issue: No ]
    Change of MSNA expressed as bursts/100 heart beats.

  • total MSNA [ Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone ] [ Designated as safety issue: No ]
    Change of MSNA expressed as burst area/min.


Other Outcome Measures:
  • Blood pressure [ Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone ] [ Designated as safety issue: No ]
    Change of blood pressure in mmHg.

  • Heart rate [ Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone ] [ Designated as safety issue: No ]
    Change of heart rate in beat per minute.

  • Cardiac output [ Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone ] [ Designated as safety issue: No ]
    Change of cardiac output in l/min.

  • Total peripheral resistance [ Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone ] [ Designated as safety issue: No ]
    Change in total peripheral resistance expressed as dyn*s/cm^5.

  • Heart rate variability. [ Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone ] [ Designated as safety issue: No ]
    Change in heart rate variability parameters in the time and frequency domain.

  • Plasma norepinephrine concentration [ Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone ] [ Designated as safety issue: No ]
    Change of plasma norepinephrine in ng/l.

  • Plasma renin concentration [ Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone ] [ Designated as safety issue: No ]
    Change of plasma renin concentration in

  • Baroreflex sensitivity [ Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone ] [ Designated as safety issue: No ]
    Change in baroreflex sensitivity expressed as ms/mmHg.

  • Inflammation parameters [ Time Frame: 3.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone ] [ Designated as safety issue: No ]
    Change of the percentage of neutrophils in induced sputum.

  • Oxidative stress parameters [ Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone ] [ Designated as safety issue: No ]
    Change of plasma malondialdehyde(MDA)concentration.

  • Correlation between inflammation, oxidative stress and cardiovascular regulation [ Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone ] [ Designated as safety issue: No ]
    Correlation coefficients between changes in parameters for inflammation and oxidative stress with changes in cardiovascular parameters.

  • Forced expiratory volume in one second (FEV1) [ Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone ] [ Designated as safety issue: No ]
    Change in FEV1 in l

  • Forced vital capacity (FVC) [ Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone ] [ Designated as safety issue: No ]
    Change in FVC in l.

  • Percentage of neutrophils in peripheral blood [ Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone ] [ Designated as safety issue: No ]
    Change of percentage of neutrophils in peripheral blood.


Estimated Enrollment: 30
Study Start Date: July 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ultrafine particles
Subjects will be exposed to ultrafine particles for three hours in an exposure chamber. During that time participants will perform intermittent bicycle ergometer training. Training intensity is adjusted individually to increase ventilation to 20 l/min/m². During exposure, heart rate will be monitored continuously via ECG. Blood pressure will be measured every 15 minutes. Ultrafine elemental carbon black particles are generated using a commercially available electric spark generator. Particle number, mass, and size distribution will be monitored during exposure.
Other: ultrafine particles
exposure to ultrafine particles
Active Comparator: ultrafine particles and ozone
Subjects will be exposed to ultrafine particles for three hours in an exposure chamber. During that time participants will perform intermittent bicycle ergometer training. Training intensity is adjusted individually to increase ventilation to 20 l/min/m². During exposure, heart rate will be monitored continuously via ECG. Blood pressure will be measured every 15 minutes. Ultrafine elemental carbon black particles are generated using a commercially available electric spark generator. Particle number, mass, and size distribution will be monitored during exposure.Ozone is generated from medical oxygen in order to maintain a concentration of 250 ppb.
Other: ultrafine particles and ozone
exposure to ultrafine particles and ozone
Placebo Comparator: clean air
Subjects will be exposed to clean air for three hours in an exposure chamber controlled for temperature, humidity, and gas/particle composition. During that time they will perform intermittent bicycle ergometer training for 15 minutes alternating with 15 minutes rest. Training intensity is adjusted individually to increase ventilation to 20 l/min/m². During exposure, heart rate will be monitored continuously via ECG. The blood pressure will be measured in time intervals of 15 minutes.
Other: clean air
Exposure to clean air.

Detailed Description:

In a randomized, double-blind, and cross-over fashion, the participants will be exposed to clean air, ultrafine particles, or ultrafine particles and ozone in an exposure chamber. The investigators will determine blood pressure, heart rate, respiration as well as cardiac output and directly record sympathetic vasomotor tone using the microneurography technique. To elucidate the underlying mechanisms through which particles and ozone affect the autonomic nervous system, the investigators will assess the local and systemic inflammatory response as well as the changes in neurotrophic factors in sputum and blood. In addition, the activation of inflammatory cells in sputum and blood will be analyzed at different points in time after exposures. Changes in sympathetic activity will be correlated with the degree of airway inflammation and oxidative stress assessed in induced sputum and blood. This study will provide important insight in the mechanisms through which air pollution, particularly ultrafine particle exposure, increases cardiovascular risk in human subjects and generate a human model for mechanistic and therapeutic studies.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Elderly man or postmenopausal woman older than 50 years of age.
  • Signed written informed consent.

Exclusion Criteria:

  • Smoker.
  • Cardiovascular and/or pulmonary disease.
  • Medication with relevant impact on autonomic system function, e. g. norepinephrine reuptake inhibitors. Stable medication with slight to moderate autonomic effects is tolerable.
  • Subject is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol.
  • Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study.
  • Subject unlikely to comply with protocol, e. g. uncooperative attitude or unlikelihood of completing the study.
  • Known hypersensitivity to ozone.
  • History of drug or alcohol abuse. Particles Study - Protocol version: October 19, 2012 14
  • Blood donation of more than 500 mL during the previous 3 months.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01914783

Contacts
Contact: Marcus May, MD +49 511 532 ext 2722 may.marcus@mh-hannover.de

Locations
Germany
Hannover Medical School Recruiting
Hannover, Germany, 30625
Contact: Marcus May, MD    +49 511 532 ext 2722    may.marcus@mh-hannover.de   
Sub-Investigator: Marcus May, MD         
Sponsors and Collaborators
Hannover Medical School
Fraunhofer-Institute of Toxicology and Experimental Medicine
  More Information

Publications:
Responsible Party: Prof. Dr. Jens Jordan, Professor Dr. med. Jens Jordan, Hannover Medical School
ClinicalTrials.gov Identifier: NCT01914783     History of Changes
Other Study ID Numbers: MHH-Particles EK-6142
Study First Received: July 30, 2013
Last Updated: July 31, 2013
Health Authority: Germany: Ethics Commission
Germany: Federal Ministry of Education and Research

Keywords provided by Hannover Medical School:
air pollution
ozone
fine particle
cytokine
chemokine
oxidative stress
inflammation
heart rate variability
autonomic nervous system
sympathetic nerve activity
plasma catecholamine

ClinicalTrials.gov processed this record on August 28, 2014